Other Seminars

Prof Alison Noble

The aim of these sessions is for the speaker to share their own experience of a career in science & how they have balanced this career with lifestyle, and for them to provide advice to scientists.
Professor Alison Noble OBE FREng is the Technikos Professor of Biomedical
Engineering in the Oxford... Read more

The aim of these sessions is for the speaker to share their own experience of a career in science & how they have balanced this career with lifestyle, and for them to provide advice to scientists.
Professor Alison Noble OBE FREng is the Technikos Professor of Biomedical
Engineering in the Oxford University Department of Engineering Science, Director of the Institute for Biomedical Engineering (IBME), and a Fellow of St Hilda’s College, Oxford. She is a Fellow of the UK IET, a Fellow of the MICCAI Society, and a Fellow of the Royal Academy of Engineering. She is also the current President of the MICCAI Society which is the international society in her field. She serves on numerous UK funding agency grant awarding and advisory panels, and a number of committees of the Royal Academy of Engineering and Royal Society. She was awarded an OBE for services to Science and Engineering in the Queen’s Birthday Honours list in June 2013.
Professor Noble is a founding director of the Biomedical Image Analysis (BioMedIA)
Laboratory based at the Oxford IBME; a multi-disciplinary research group working in the area of biomedical imaging and image analysis, an important sub-discipline of modern biomedical engineering. She heads a large research activity in cardiovascular image analysis, women’s health imaging (obstetrics and perinatal care) and microscopy image analysis. She is also Chief Technology Officer of Intelligent Ultrasound Ltd, a spin-out company from her laboratory. Throughout her career she has combined research with training early career researchers, playing an influential role in setting up biomedical engineering education programmes at the undergraduate and postgraduate level at Oxford, and personally having supervised or co-supervised 49 PhD students to successful completion to-date.

Dr Kim Dalziel

Self-reported information on past utilization of health care is routinely used by many health researchers. However, the recall period of questions varies widely between surveys and this variation may affect the results of analyses. This seminar examines the role of length of recall period, mainly... Read more

Self-reported information on past utilization of health care is routinely used by many health researchers. However, the recall period of questions varies widely between surveys and this variation may affect the results of analyses. This seminar examines the role of length of recall period, mainly using a large experiment conducted in Sweden of self-reported hospitalizations of respondents. Respondents were asked a question on the number of nights they spent in hospital in which the recall period varied between one and twelve months. Our findings have conflicting implications for survey design as the preferred recall length depends on the objectives of the analysis. We will conclude by outlining planned experiments to build a better evidence base for designing surveys.

Dr Adele Murrell

Adele Murrell investigates a wide range questions in epigenetics, with a particular focus on cancer. Her work includes analysis of epigenetic reprogramming during metastases. When cells metastasise from a primary cancer site to a new site, they undergo epigenetic reprogramming events that enable... Read more

Adele Murrell investigates a wide range questions in epigenetics, with a particular focus on cancer. Her work includes analysis of epigenetic reprogramming during metastases. When cells metastasise from a primary cancer site to a new site, they undergo epigenetic reprogramming events that enable them to migrate, infiltrate, adapt and colonise a new environment. A future goal of her work is to identify the triggers of these epigenetic changes with a view to prevent secondary tumour formation in cancer.

Dr Simon Kollnberger

Chronic immune inflammation results from a failure to resolve persistent inflammatory stimuli. The resolution of inflammation is critically dependent on the carefully balanced orchestration of immune responses. “Inhibitory” KIR immune receptor interactions with HLA-class I have been... Read more

Chronic immune inflammation results from a failure to resolve persistent inflammatory stimuli. The resolution of inflammation is critically dependent on the carefully balanced orchestration of immune responses. “Inhibitory” KIR immune receptor interactions with HLA-class I have been implicated in diverse chronic inflammatory disorders including spondyloarthritis, Crohn’s disease and Pemphigus vulgaris. I will discuss how "inhibitory" KIR immune receptor interactions could promote inflammation using knowledge gained from our studies on HLA-B27 binding to immune receptors.

Professor Martin Dufva

Micro- and nanotechnology is used today as a base for a whole range of modern biomedical assays. Prime examples are next generation sequencing and single cell sample preparation. Micro technology is also used extensively to mimic physiological relationships of cell organisation (organ-on-a-chip)... Read more

Micro- and nanotechnology is used today as a base for a whole range of modern biomedical assays. Prime examples are next generation sequencing and single cell sample preparation. Micro technology is also used extensively to mimic physiological relationships of cell organisation (organ-on-a-chip) as well as cellular based high throughput screening. Micro and nanotechnology enables miniaturisation, precise spatial control, convenient rapid self assembly of samples, and not the least automation. However, these benefits come at price of other regimes for molecular mass transport, other materials used and practical issues to use rather complex devices. With examples of my own research regarding single molecule counting, organ modelling and high throughput technologies for drug development and diagnostics, I will highlight advantages and disadvantages of employing micro and nanotechnologies in biomedical assays. While these novel technologies are here to stay, they are far from the well known polystyrene cell culture dish, the Eppendorff tube, and the pipette which the vast majority of biomedical research is based on. Therefore, employing these new methods have far ranging implications in assay design but also to what extent data gathered with these new methods can be compared to the current literature.

Transcription by RNA polymerase in bacteria requires specific promoter recognition by σ factors. The major variant ••••• factor (sigma54) initially forms a transcriptionally silent complex requiring specialised ATP-dependent activators that belong to AAA+ protein family for initiation. I will present our recent crystal structure of the 450 kDa RNAP-σ54 holoenzyme at 3.8 Å, which reveals molecular details of ••••••• and its interactions with RNAP. The structure explains how ••••••• targets different regions in RNAP to exert its inhibitory function. In addition, I will explain how the AAA activator uses its ATPase activity to activate RNAP-sigma54 holoenzyme. I will also compare different RNAP systems and suggest the existence of evolutionarily conserved regulatory hotspots within RNAPs that can be targeted by a diverse range of mechanisms to fine tune transcription.

Dr Dimitrios Davalos

Dr. Davalos investigates how microglia become activated when the brain vasculature is compromised, and how microglial responses affect neuronal function in physiological or pathological conditions. He performed the first in vivo imaging study of microglia and has developed novel methods for... Read more

Dr. Davalos investigates how microglia become activated when the brain vasculature is compromised, and how microglial responses affect neuronal function in physiological or pathological conditions. He performed the first in vivo imaging study of microglia and has developed novel methods for intravital microscopy of the brain and spinal cord in living mice. His research combines cutting-edge imaging techniques with molecular, cellular and genetic approaches to study the interactions between blood vessels, neurons, and glia, and understand how their relationships change between health and disease.

Prof. Raghu Machiraju

For a complex disease such as cancer, there are many different ways to characterise it using genotyping, gene expression profiling and histology, and clinical sub-typing. These characterisations and sub-typing often lead to different and heterogeneous stratification of patients with varying power... Read more

For a complex disease such as cancer, there are many different ways to characterise it using genotyping, gene expression profiling and histology, and clinical sub-typing. These characterisations and sub-typing often lead to different and heterogeneous stratification of patients with varying power of prognosis and prediction for effective clinical treatment. This issue particular has become prominent given the availability of several data repositories including The Cancer Genome Atlas (TCGA). In these repositories multiple types of molecular, image, and clinical data are available for analyses. There is a need for developing innovative computational algorithms for integrating multiple types of genomic and phenotype data.
We have recently developed novel learning and visualisation algorithms to complete workflows for integrative genomics. One particular challenge is the use of mixed data types namely categorical (e.g., clinical traits) and numerical data (expression). I will describe our response in the form of regularised consensus algorithm whereby clustering in the molecular expression space modulates the distributions in the categorical clinical space. Another, challenge is the extraction of suitable features from large histology images for purposes of summarisation and correlative studies. I will describe a workflow that identifies tissue compartments (epithelium, stroma), extracts features, and then correlates them with genetic signatures. Finally, I will briefly describe our recent efforts in correlating proteomic and transcriptomic data captured in the NCI-60 panel through the use of co-expression networks. This work has been conducted in collaboration with Prof. Kun Huang and is supported by the National Science Foundation, and the National Institutes of Health.

Dr Jane Hirst

The first 1000 days of life is crucial to establish foundations for growth, metabolism and development. With over 100 different fetal growth charts in use, diagnosis of ‘small for gestational age’ depends more upon location and choice of chart, than failure to attain physiological growth.... Read more

The first 1000 days of life is crucial to establish foundations for growth, metabolism and development. With over 100 different fetal growth charts in use, diagnosis of ‘small for gestational age’ depends more upon location and choice of chart, than failure to attain physiological growth. Consequently in 2015 we have few effective interventions for this major global health problem. The International Fetal and Newborn Growth consortium for the 21st century (INTERGROWTH-21st) was established to define optimal growth and development and the conditions required for this to occur. The INTERGROWTH-21st study was conducted in eight diverse international settings selected as social, nutritional and health care needs of mothers were largely met. In 2014 the study published it’s primary findings that under these conditions, linear fetal growth from 9 weeks gestation is strikingly similar around the world. International standards for CRL, fetal growth and newborn size at birth have now been released. The challenge will now be in implementing the standards and addressing the burden of nutritional problems evident from birth.

Audience: Members of the University only

Organisers: Francois Van Loggerenberg

Refreshments are provided, please arrive promptly. Space is limited; first come, first served!

Prof. James Cross

Prof. James (Jay) Cross is Professor of Comparative Biology & Experimental Medicine, Biochemistry & Molecular Biology, Medical Genetics, and Obstetrics & Gynaecology at the University of Calgary. He was the founding Director of the Institute of Maternal & Child Health a multi-disciplinary institute... Read more

Prof. James (Jay) Cross is Professor of Comparative Biology & Experimental Medicine, Biochemistry & Molecular Biology, Medical Genetics, and Obstetrics & Gynaecology at the University of Calgary. He was the founding Director of the Institute of Maternal & Child Health a multi-disciplinary institute focused on biomedical, clinical and social aspects of child health and development. He also founded the Training Program in Genetics, Child Development & Health, and the Clara Christie Centre for Genomics and Modeling of Human Disease. Dr. Cross has published over 120 primary research articles and book chapters and is an internationally recognized expert in the areas of animal reproduction, embryology, stem cell biology, and molecular genetics particularly in the areas of embryo implantation, placental development and maternal adaptations to pregnancy. He received the Pioneer Award from the Frontiers in Reproduction Program at the Marine Biology Laboratory, Wood’s Hole USA, and is a Fellow of both the Canadian Academy of Health Sciences and the Royal Society of Canada.

Dr Josep Forment

Recent adaptation of the CRISPR/Cas9 bacterial system to facilitate manipulation of mammalian genomes has provided a real breakthrough for genome editing applications. Development of whole-genome CRISPR libraries with the aim of generating gene knockouts for every single coding sequence has allowed... Read more

Recent adaptation of the CRISPR/Cas9 bacterial system to facilitate manipulation of mammalian genomes has provided a real breakthrough for genome editing applications. Development of whole-genome CRISPR libraries with the aim of generating gene knockouts for every single coding sequence has allowed forward genetic screening in mammalian cells with unprecedented efficiency and versatility. CRISPR/Cas9 approaches, however, rely on phenotypes associated with loss-of-function mutations. Single-nucleotide variations (SNVs), on the other hand, have the potential to uncover not only loss-of-function phenotypes (by generating nonsense mutations, for example) but also gain-of-function phenotypes through missense mutations. In addition, they produce valuable information regarding functionally important domains of the affected gene product, as SNVs causative of a particular phenotype tend to cluster around specific regions of the amino acid sequence of the encoded protein. SNV-based approaches in mammalian cells, however, have been hindered by the diploid nature of their genomes, a fact that complicates the establishment of straightforward genotype-to-phenotype correlations. In this talk I will discuss how we apply CRISPR/Cas9 genetic screening to further understand the DNA-damage response in mouse embryonic stem cells (mESCs), and I will also introduce the use of haploid mESCs to perform SNV-based forward genetic screens.

Dr Tony D. Southall

Neurons of the central nervous system possess very diverse morphologies, neurotransmitter identities, electrical properties and preferences for synaptic partners. How are all these different properties specified and maintained? We are applying the new Targeted DamID (TaDa) (Southall et al., 2013)... Read more

Neurons of the central nervous system possess very diverse morphologies, neurotransmitter identities, electrical properties and preferences for synaptic partners. How are all these different properties specified and maintained? We are applying the new Targeted DamID (TaDa) (Southall et al., 2013) technique to profile the transcriptional state of specific neuronal populations in vivo, with the aim of identifying key transcriptional regulators. A comparison of cholinergic, GABAergic and glutamatergic neurons has revealed a number of transcription factors that are specific or highly enriched in the respective cell types. Initial characterisation of candidates has identified an Ets transcription factor that inhibits cholinergic fate. Furthermore, our TaDa data suggests that this type of cross-repressive mechanism might be common for neurotransmitter specification and maintenance.
We are also interested in dedifferentiation in the nervous system, and are investigating the mechanisms by which the transcription factor Lola prevents neurons reverting to a neural stem cell fate (Southall et al., 2014). Interestingly, we have recently identified a small ORF peptide, encoded by a long non-coding RNA, which interacts with Lola and may regulate its function.

Criselle D'Souza

Mucosal Associated Innate T (MAIT) cells are innate like T lymphocytes that express a semi-invariant TCR and are restricted by the non-classical MHC class I-related molecule, MR1. These cells are predominantly found at mucosal surfaces and are activated by a novel class of antigens, intermediates... Read more

Mucosal Associated Innate T (MAIT) cells are innate like T lymphocytes that express a semi-invariant TCR and are restricted by the non-classical MHC class I-related molecule, MR1. These cells are predominantly found at mucosal surfaces and are activated by a novel class of antigens, intermediates of the riboflavin synthesis pathway that are produced by certain class of bacteria and yeasts.
We have examined whether MAIT cells play a role in the pathology of chronic H. pylori infection. We have recently developed highly specific MR1 tetramers that have been used to detect and characterize MAIT cells in mice. Our studies show that MAIT cells play a key role in the regulation of gastric inflammation in H. pylori infection. Using a mouse model that first enriches MAIT cells in the lung, we show repopulation of MAIT cells to other mucosal sites including the stomach. On challenge with H. pylori, these mice develop an accelerated inflammatory response leading to atrophic gastritis. In our model, MAIT cells have a pathogenic rather than protective effect. We are working to understand their role with a view to therapeutic intervention.

Dr Susanne la Fleur

Aberrant feeding behavior can lead to obesity and obesity-related medical consequences, such as insulin resistance and diabetes. Although alterations in glucose metabolism (i.e. insulin resistance), in the presence of excessive fat tissue are often explained by the consequences of dysfunctional... Read more

Aberrant feeding behavior can lead to obesity and obesity-related medical consequences, such as insulin resistance and diabetes. Although alterations in glucose metabolism (i.e. insulin resistance), in the presence of excessive fat tissue are often explained by the consequences of dysfunctional adipose tissue, evidence is emerging that also altered brain functions might be an important determinant of insulin resistance. Data will be presented on how feeding behavior and obesity interact with brain circuitry and how these interactions affect glucose metabolism.

Dr Eric Brown

Dr. Brown studies the mechanisms that safeguard genome integrity during replication and investigates how defects in these processes impact tissue homoeostasis, cancer risk, and cancer treatment. His work has focused on three specific areas: 1) cell extrinsic mechanisms that limit the accumulation... Read more

Dr. Brown studies the mechanisms that safeguard genome integrity during replication and investigates how defects in these processes impact tissue homoeostasis, cancer risk, and cancer treatment. His work has focused on three specific areas: 1) cell extrinsic mechanisms that limit the accumulation replication stress-induced DNA damage in tissues[1,2], 2) the promise of ATR-CHK1 pathway inhibitors as cancer treatments[1-4], and 3) the role of ATR in preventing replication fork collapse and genomic instability[5,6]. In regards to the third research area, Dr. Brown’s laboratory has studied on how layered networks of checkpoint and repair genes cooperate to suppress double strand breaks in S phase and has identified novel synthetic lethal interactions for potential use in cancer treatment. His laboratory’s most recent study in this area implicates the AURKA-PLK1 pathway and the SUMO-targeted Ubiquitin ligase RNF4 as driving forces in replication fork collapse when ATR function is compromised[6]. This work and Dr. Brown’s demonstration that ATR-CHK1 inhibition is synthetically lethal with oncogene expression[3,4] have remarkable potential for clinical application, particularly in terms of the breadth of cancers in which ATR and CHK1 inhibitors may be applied.

Professor Zoi Lygerou

Zoi Lygerou is Professor of Biology at Patras Medical School in Greece, Director of Studies of the Interdepartmental Postgraduate Program "Life Sciences Informatics" and member of the Directing Board for Research of the University of Patras. Following a degree in Biology from the University of... Read more

Zoi Lygerou is Professor of Biology at Patras Medical School in Greece, Director of Studies of the Interdepartmental Postgraduate Program "Life Sciences Informatics" and member of the Directing Board for Research of the University of Patras. Following a degree in Biology from the University of Athens, a PhD at the EMBL in Heidelberg, and a postdoc at the London Research Institute, Zoi returned to Greece to head a research team at the University of Patras. She studies the control mechanisms which safeguard genomic stability by ensuring once per cell cycle replication in eukaryotic cells and how defects in this control may lead to tumorigenesis. Her team combines molecular-cell biology studies in human cells, genetic studies in fission yeast, analyses of tumor specimens, advanced live cell imaging and modelling of biological networks. She is the recipient of an ERC Consolidator Grant, became an EMBO Young Investigator in 2000 and an EMBO member in 2014.
PUBLICATIONS:
Rapsomaniki, M. A., Cinquemani, E., Giakoumakis, N. N., Kotsantis, P., Lygeros, J., & Lygerou, Z. (2015). Inference of protein kinetics by stochastic modeling and simulation of fluorescence recovery after photobleaching experiments. Bioinformatics, 2015 Feb 1;31(3):355-62.
Symeonidou IE, Kotsantis P, Roukos V, Rapsomaniki MA, Grecco HE, Bastiaens P, Taraviras S, Lygerou Z. (2013) Multi-step loading of human Mini-Chromosome Maintenance Proteins in live human cells. J Biol. Chem. 288(50): 35852-67
Pefani DE, Dimaki M, Spella M, Karantzelis N, Mitsiki E, Kyrousi C, Symeonidou IE, Perrakis A, Taraviras S, Lygerou Z. (2011) Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression. J. Biol. Chem. 286:23234-46
Roukos V, Kinkhabwala A, Colombelli J, Kotsantis P, Taraviras S, Nishitani H, Stelzer E, Bastiaens P, and Lygerou Z (2011) Dynamic Recruitment of the Licensing Factor Cdt1 to Sites of DNA Damage J. Cell Science. 124:422-432
J. Lygeros, K. Koutroumpas, S. Dimopoulos, I. Legouras, P. Kouretas, C. Heichinger, P. Nurse, Z. Lygerou (2008) Stochastic hybrid modelling of DNA replication across a complete genome. Proc Natl Acad Sci USA. 105:12295-12300.